ABSTRACT: OBJECTIVES:We sought to describe trends in the use of preprocedural P2Y12 inhibitors and their clinical impact in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND:Oral P2Y12 inhibitors are ubiquitously used medications; however, the specific timing of initial P2Y12 inhibitor administration remains intensely debated. METHODS:Our study population comprised 74,053 consecutive patients undergoing PCI at 47 hospitals in Michigan from January 2013 through June 2015. In-hospital outcomes included stent thrombosis, bleeding, need for transfusion, and death. Hierarchical logistic regression, propensity matching, and targeted maximum likelihood estimation were used to adjust for baseline patient differences and clustering, and to minimize bias. RESULTS:Of 24,733 patients who received a preprocedural P2Y12 inhibitor, 82% received clopidogrel, 8% prasugrel, and 10% ticagrelor. Preprocedural administration of P2Y12 inhibitors declined during the study (49.3% to 24.8%; P<.001), and varied greatly across hospitals (14.5%-95.9%). No significant differences in outcomes were observed between patients receiving preprocedural clopidogrel and a matched cohort of those not receiving any preprocedural P2Y12 inhibitor (stent thrombosis: adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 0.30-7.84; bleeding: OR, 0.96; 95% CI, 0.63-1.46; transfusion: OR, 1.03; 95% CI, 0.69-1.55; and death: OR, 0.95; 95% CI, 0.38-2.37). Similar findings were demonstrated for preprocedural ticagrelor and prasugrel. Results from a subgroup analysis of patients with non-ST segment elevation acute coronary syndrome (n = 28,072) were consistent with the overall findings. CONCLUSIONS:There was a substantial decline in the rate of preprocedural P2Y12 inhibitor administration during the study. Furthermore, there were no significant differences in outcomes between patients treated with preprocedural P2Y12 inhibitors and those who were not.